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      Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults

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          Abstract

          Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57–85 were studied in 2005–6 (Wave 1) and their mortality determined in 2010–11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a “dose-dependent” effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.

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          Most cited references38

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          Frailty in older adults: evidence for a phenotype

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            Use of multiple biomarkers to improve the prediction of death from cardiovascular causes.

            The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors. Copyright 2008 Massachusetts Medical Society.
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              On the Variances of Asymptotically Normal Estimators from Complex Surveys

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                1 October 2014
                : 9
                : 10
                : e107541
                Affiliations
                [1 ]Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, Illinois, United States of America
                [2 ]Department of Health Studies, The University of Chicago, Chicago, Illinois, United States of America
                [3 ]Department of Comparative Human Development and The Institute for Mind and Biology, The University of Chicago, Chicago, Illinois, United States of America
                [4 ]The Center on the Demography and Economics of Aging, National Opinion Research Center, The University of Chicago, Chicago, Illinois, United States of America
                Technical University of Dresden Medical School, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JMP MKM. Performed the experiments: LPS MKM. Analyzed the data: KEW JMP MKM LPS. Contributed reagents/materials/analysis tools: DWK LPS. Wrote the paper: JMP. Supervised the study: JMP MKM LPS. Provided critical revision of the manuscript for important intellectual content: KEW DWK LPS MKM.

                Article
                PONE-D-14-20307
                10.1371/journal.pone.0107541
                4182669
                25271633
                472cd573-53b2-4d8c-b645-07b002df4e2b
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 May 2014
                : 15 August 2014
                Page count
                Pages: 9
                Funding
                The National Institutes of Health, including the National Institute on Aging, the Office of Women's Health Research, the Office of AIDS Research, and the Office of Behavioral and Social Sciences Research (AG021487, AG033903-01, and AG030481). Support was also provided by the National Institute on Aging (AG029795, AG036762, and T32000243), the McHugh Otolaryngology Research Fund, the American Geriatrics Society, The Center on the Demography and Economics of Aging, a Mellon Foundation Social Sciences Dissertation-Year Fellowship, and the Institute of Translational Medicine at The University of Chicago (KL2RR025000 and UL1RR024999). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Geriatrics
                Neurology
                Otorhinolaryngology
                People and Places
                Demography
                Custom metadata
                The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data are available from the Inter-university Consortium for Political and Social Research at http://www.icpsr.umich.edu/icpsrweb/landing.jsp. Users interested in obtaining these data from must request and complete the NSHAP Restricted Data Use Agreement form available at that web address.

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